Apoptosis is a form of cell death that is carried out by a specialized intrinsic machinery. Although the knowledge about the biochemical mechanisms of apoptosis is fragmentary, it appears that signalling pathways that regulate apoptosis converge on a conserved machinery that disassembles a cell. An essential part of this machinery is a family of proteases related to interleukin-1B-converting enzyme (ICE) (Lazebnik, Y. A., et al., Proc. Natl. Acad. Sci. USA, 92:9042-9046 (1995); (Lazebnik, Y. A., et al ., Nature, 371:346-347 (1994); Nicholson, D. W., et al., Nature, 376:37-43 (1995); Yuan, J., et al., Cell, 641-652:641-652 (1993)). ICE-like proteases (ILPS) are expressed as inactive pro-enzymes that have to be activated to cleave their substrates and to contribute to apoptosis (Horvitz, H. R., et al., Cold Spring Harb. Symp. Quant. Biol., 59:377-385 (1994); Oltvai, Z. N. and Korsmeyer, S. J., Cell, 79:189-192 (1994)).
Cancer chemotherapy kills cells by induction of apoptosis (Lowe, S. W., et al., Cell, 74:957-967 (1993); Fisher, D. E., Cell, 78:539-542 (1994)). Defects of apoptosis common in cancer cells contribute to tumor regression and appear to be responsible for the failure of current cancer chemotherapy. Alternatively excess apoptosis can lead to neurodegenerative diseases (e.g., Huntington's Disease, Alzheimers Disease).
Therefore, more effective chemotherapeutic agents are needed.